Parasitic nematodes disproportionately affect the poorest individuals in the world. The soil-transmitted intestinal nematodes, Ascaris lumbricoides, hookworm (Necator americanus and Ancylostoma duodenale) and whipworm (Trichuris trichiura), have a staggering global burden: up to 1.5 billion people are chronically infected with one of these nematodes by some estimates. Infection often begins in childhood and can have myriad consequences that persist into adulthood. In children, these pathogens cause malnourishment, can stunt intellectual and physical growth, and have been directly linked to school absenteeism. Thus, these infectious diseases can have a profound impact on the economic stability of both individuals and communities.
Another major intestinal pathogenic nematode, Strongyloides stercoralis, has the unique ability to replicate inside the human host, and thus it can persist for decades via a process called autoinfection. Although accurate estimates are difficult to determine, as many as 500 million people may be infected with this pathogen, which is a particular problem in the setting of immune compromise when Strongyloides can cause overwhelming infection and death.
The filarial nematodes comprise a separate class of tissue-dwelling helminths that are be transmitted by the bite of an insect vector. This group includes the etiological agent of river blindness (Onchocerca volvulus), lymphatic filariasis (Wucheria bancrofti and Brugia sp.) and loiaisis (Loa loa), which together have an enormous socioeconomic impact in the developing world as the cause of preventable blindness and debilitating edema of the lower extremities and genitalia.
Despite repeated calls for action by the World Health Organization, these neglected tropical diseases remain a scourge of humanity. Preventative chemotherapy through mass treatment of susceptible populations is a possible solution to this public health crisis; however, no single agent is active against all pathogenic nematodes. For example, albendazole is the only currently available medication with an adequate efficacy and safety profile for single-dose mass administration. It is believed effective against Ascaris, but has variable activity against hookworm, and no activity against whipworm. In addition, albendazole is not efficacious enough toward Strongyloides and the filarial nematodes to enable single dose treatment.
What is urgently needed in the art are new pharmaceutical therapies that are capable of broad spectrum nematode clinical effectiveness.